This research is aimed at the elucidation of the biological function and genetic control of the polydisperse circular DNA complement of Bacillus megaterium. The specific objectives involve (1) the characterization of the mode of production of these elements; (2) the determination of their physiological function in the cell and (3) a test of the possibility that these elements reflect a novel regulatory mechanism for DNA replication and/or gene expression which may provide clues to an understanding of certain types of neoplasias in higher organisms. The research involves the use of electron microscopic analysis, including partial denaturation and heteroduplex techniques, and cleavage of specific circular DNA classes with site-specific restriction endonucleases in order to determine the relationships between these molecules. DNA-DNA hybridization will also be employed as will sedimentation velocity procedures for characterization of these elements. Specific inhibitors will be employed to determine the mode of production. Their biological properties will be assessed by attempts to isolate auxotrophic mutants as well as genetic variants defective in megacin production and other properties, and by attempts to transfer these elements to other bacteria by genetic transformation.